Work of the SCOR has demonstrated the key role of inherited variation in renal salt handling in blood pressure variation in humans. These findings from rate Mendelian diseases raise the question of whether more common variants in genes of this same pathway alter blood pressure in the general population. This project investigates the causes of inherited variation in blood pressure, end-stage renal disease and left ventricular hypertrophy. Study populations are 4100 members of the Framingham Heart Study and multiplex kindreds with end-stage renal disease recruited from the GAMBRO dialysis centers. Specific Aim 1 will investigate the impact of single nucleotide polymorphisms in genes in which mutations cause inherited forms of high or low blood pressure on blood pressure and LVH in 4000 subjects from the Framingham Heart Study. This Study has substantial power to detect even modest effects imparted by these variants. Specific Aim 2 will work toward the positional cloning of a blood pressure locus on chromosome 17 that demonstrated a lod score of 4.7 for linkage to systolic blood pressure in families from Framingham Study.